Citations 7
Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2
Gaudet, Mia M. , Antoniou, Antonis C. , Ramus, Susan J. , Kuchenbaecker, Karoline , Soucy, Penny, Chen, Xiaoqing, Kirchhoff, Tomas , McGuffog, Lesley, Barrowdale, Daniel , Healey, Sue, Sinilnikova, Olga M., Andrulis, Irene L. , Özçelik, Hilmi, Mulligan, Anna Marie , Thomassen, Mads , Gerdes, Anne‐Marie , Jensen, Uffe Birk , Skytte, Anne‐Bine , Kruse, Torben A., Caligo, Maria A. , Wachenfeldt, Anna von , Barbany, Gisela , Loman, Niklas, Soller, Maria , Ehrencrona, Hans , Karlsson, Per , Nathanson, Katherine L. , Rebbeck, Timothy R., Jakubowska, Anna , Lubiński, Jan , Jaworska, Katarzyna, Durda, Katarzyna, Złowocka, Elżbieta, Huzarski, Tomasz , Byrski, Tomasz , Cybulski, Cezary, Górski, Bohdan , Osório, Ana , Durán, M. , Tejada, María‐Isabel , Hamann, Ute, Hogervorst, Frans B.L., Os, Theo A. van, Leeuwen, Flora E. van , Meijers‐Heijboer, Hanne , Blok, Marinus J. , Kets, Marleen, Hooning, Maartje J. , Oldenburg, Rogier A., Ausems, Margreet G.E.M. , Peock, Susan, Frost, Debra, Ellis, Steve D., Platte, Radka, Fineberg, Elena, Evans, D. Gareth , Jacobs, Chris , Eeles, Rosalind A. , Adlard, Julian , Davidson, Rosemarie, Eccles, Diana M., Cole, Trevor, Paterson, Joan, Brewer, Carole, Douglas, Fiona, Hodgson, Shirley V. , Walker, Lisa, Porteous, Mary, Kennedy, M. John, Side, Lucy, Bove, Betsy, Fassy-Colcombet, Marion, Castéra, Laurent , Cornelis, François, Mazoyer, Sylvie , Léoné, Mélanie, Boutry‐Kryza, Nadia, Paillerets, Brigitte Bressac–de , Coupier, Isabelle, Delnatte, Capucine, Akloul, Linda, Lynch, Henry T., Snyder, Carrie, Daly, Mary B., Terry, Mary Beth , John, Esther M. , Miron, Alexander, Southey, Melissa C. , Goldgar, David E., Singer, Christian F., Rappaport, Christine , Tea, Muy‐Kheng M., Fink-Retter, Anneliese, Hansen, Thomas van Overeem , Nielsen, Finn C., Arason, Aðalgeir , Vijai, Joseph , Shah, Sohela, Sarrel, Kara , Piedmonte, Marion, Phillips, Kelly, Basil, Jack, Rubinstein, Wendy S. , Boggess, John F., Wakeley, Katie, Montagna, Marco , Imyanitov, Evgeny N., Janavičius, Ramūnas , Lázaro, Conxi , Blanco, Ignacio , Feliubadaló, Lídia , Brunet, Joan , Gayther, Simon A. , Odunsi, Kunle , Walsh, Christine , Oláh, Edith , Teo, Soo‐Hwang , Ganz, Patricia A. , Beattie, Mary, Rensburg, Elizabeth J. van , Dorfling, Cecelia M., Dı́ez, Orland , Kwong, Ava , Schmutzler, Rita K., Wappenschmidt, Barbara, Engel, Christoph , Meindl, Alfons , Ditsch, Nina , Arnold, Norbert , Heidemann, Simone , Niederacher, Dieter , Preisler‐Adams, Sabine, Gadzicki, Dorothea, Varon-Mateeva, Raymonda, Deißler, Helmut , Gehrig, Andrea, Sutter, Christian , Kast, Karin, Fiebig, Britta, Heinritz, Wolfram, Caldes, Trinidad, Hoya, Miguel de la , Muranen, Taru , Nevanlinna, Heli , Spurdle, Amanda B. , Ding, Yuan Chun , Lindor, Noralane M. , Fredericksen, Zachary, Pankratz, V. Shane , Peterlongo, Paolo , Manoukian, Siranoush , Peissel, Bernard , Zaffaroni, Daniela , Barile, Monica, Bernard, Loris, Viel, Alessandra , Giannini, Giuseppe , Varesco, Liliana , Radice, Paolo , Greene, Mark H. , Mai, Phuong L., Easton, Douglas F., Chenevix‐Trench, Georgia , Offit, Kenneth, Simard, Jacques , Durocher, Francine , Eccles, Diana , Thorne, Heather , Phillips, Kelly‐Anne , Couch, Fergus J. , Beesley, Jonathan , Chen, Xiaoqing, Wang, Xianshu , Lee, Andrew , Domchek, Susan M. , Gronwald, Jacek , Benı́tez, Javier , Wijnen, Juul , Eccles, Diana M., Cook, Jackie A , Morrison, Patrick J. , Kennedy, M. John, Godwin, Andrew K. , Stoppa‐Lyonnet, Dominique , Caron, Olivier , Pujol, Pascal , Buys, Saundra S. , Chung, Wendy K. , Hopper, John L. , Singer, Christian F. , Robson, Mark E. , Phillips, Kelly, Toland, Amanda Ewart , Agata, Simona , Isaacs, Claudine , Pharoah, Paul D.P. , Karlan, Beth Y. , Meindl, Alfons , Varon-Mateeva, Raymonda, Caldes, Trinidad, Tischkowitz, Marc D. , Neuhausen, Susan L. , Mai, Phuong L., Nevanlinna, H , Caligo, Maria A , Peterlongo, Paolo , Ramus, Susan J , Spurdle, Amanda B , Teo, Soo H , van Rensburg, Elizabeth J , Eccles, Diana , de la Hoya, Miguel , Diez, Orland , Radice, Paolo , Adlard, Julian , Arnold, Norbert , Brunet, Joan , Eeles, Rosalind A , Ehrencrona, Hans , Evans, D Gareth , John, Esther M , Joseph, Vijai , Southey, Melissa C , Jakubowska, Anna , Muranen, Taru A , Nathanson, Katherine L , Arason, Adalgeir , Barrowdale, Daniel , Engel, Christoph , Lazaro, Conxi , Montagna, Marco , Viel, Alessandra , Simard, Jacques , Chenevix-Trench, Georgia , Huzarski, Tomasz , Feliubadaló, Lidia , Hansen, Thomas van Overeem , Manoukian, Siranoush , Lubinski, Jan , Phillips, Kelly-Anne , Terry, Mary Beth , Kwong, Ava
Cancer Epidemiology, Biomarkers & Prevention | March 29, 2012 | Volume: 21 | Issue: 4 | Pages: 645-657
Abstract Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07–1.27; P = 7.42 × 10−4] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73–0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94–1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05–1.29; P = 3.8 × 10−4) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10–1.52; P = 1.8 × 10−3). Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(4); 645–57. ©2012 AACR.
Common Variation in Nemo-Like Kinase Is Associated with Risk of Ovarian Cancer
Stevens, Kristen N., Kelemen, Linda E., Vierkant, Robert A. , Fredericksen, Zachary, Armasu, Sebastian M. , Tsai, Ya-Yu, Narod, Steven A., Phelan, Catherine M., Sutphen, Rebecca , Birrer, Michael J. , Schildkraut, Joellen M. , Sellers, Thomas A. , Goode, Ellen L. , Purrington, Kristen S. , Wang, Xianshu , Fridley, Brooke L. , Berchuck, Andrew , Couch, Fergus J. , Vierkant, Robert A , Purrington, Kristen S
Cancer Epidemiology, Biomarkers & Prevention | March 7, 2012 | Volume: 21 | Issue: 3 | Pages: 523-528
Abstract Background: Overexpression of mitotic kinases has been associated with prognosis, histologic grade, and clinical stage in ovarian cancer, but the relationship between inherited variation in these genes and ovarian cancer risk has not been well defined. Methods: We measured associations between 397 single nucleotide polymorphisms (SNPs) from 67 mitotic kinases and invasive epithelial ovarian cancer risk in two case–control studies (n = 671 cases; n = 939 controls). Thirty-six candidate SNPs (P < 0.05) were assessed in a replication analysis consisting of three additional studies (n = 1,094 cases; n = 829 controls). Results: In initial analysis, thirty-six SNPs were suggestive of association with risk of serous ovarian cancer, all subtypes of ovarian cancer, or both (P < 0.05). Replication analyses suggested an association between rs2125846 in the Nemo-like kinase (NLK) gene and ovarian cancer (serous OR = 1.36, 95% CI: 1.11–1.67, P = 1.77 × 10−3; all subtypes OR = 1.30, 95% CI: 1.08–1.56, P = 2.97 × 10−3). Furthermore, rs2125846 was associated with risk in the combined discovery and replication sets (serous OR = 1.33, 95% CI: 1.15–1.54; all subtypes OR = 1.27, 95% CI: 1.12–1.45). Conclusions: Variation in NLK may be associated with risk of invasive epithelial ovarian cancer. Further studies are needed to confirm and understand the biologic relationship between this mitotic kinase and ovarian cancer risk. Impact: An association between SNPs in NLK and ovarian cancer may provide biologic insight into the development of this disease. Cancer Epidemiol Biomarkers Prev; 21(3); 523–8. ©2012 AACR.
19p13.1 Is a Triple-Negative–Specific Breast Cancer Susceptibility Locus
Stevens, Kristen N., Fredericksen, Zachary, Vachon, Celine M. , Margolin, Sara , Lindblom, Annika , Nevanlinna, Heli , Greco, Dario , Aittomäki, Kristiina, Blomqvist, Carl , Chang‐Claude, Jenny , Vrieling, Alina , Flesch‐Janys, Dieter, Sinn, Hans‐Peter , Wang‐Gohrke, Shan , Nickels, Stefan , Brauch, Hiltrud , Ko, Yon‐Dschun, Fischer, Hans‐Peter , Schmutzler, Rita K., Meindl, Alfons, Bartram, Claus R., Schott, Sarah , Engel, Christoph , Weaver, JoEllen , Sharma, Priyanka , Brenner, Hermann , Stegmaier, Christa, Miron, Penelope , Yannoukakos, Drakoulis , Stavropoulou, Alexandra , Fountzilas, George , Swann, Ruth , Dwek, Miriam , Perkins, Annie, Zamora, María Pilar, Bojesen, Stig E. , Nielsen, Sune F. , Nordestgaard, Børge G. , Flyger, Henrik, Guénel, Pascal , Truong, Thérèse , Ménégaux, F. , Cordina‐Duverger, Emilie, Burwinkel, Barbara , Marmé, Frederick, Schneeweiß, Andreas , Sohn, Christof , Sawyer, Elinor J. , Tomlinson, Ian , Kerin, Michael J. , Peto, Julian , Johnson, Nichola , dos‐Santos‐Silva, Isabel , Fasching, Peter A. , Beckmann, Matthias W. , Hartmann, Arndt , Ekici, Arif B. , Lophatananon, Artitaya, Muir, Kenneth , Puttawibul, Puttisak, Wiangnon, Surapon , Schmidt, Marjanka K. , Braaf, Linde M., Rosenberg, Efraim H. , Hopper, John L. , Apicella, Carmel, Park, Daniel J. , Southey, Melissa C. , Swerdlow, Anthony J. , Ashworth, Alan , Orr, Nicholas, Schoemaker, Minouk J. , Dur, Christina Clarke, Shen, Chen‐Yang , Yu, Jyh-Cherng, Hsu, Huan-Ming, Hsiung, Chia‐Ni , Hamann, Ute , Dünnebier, Thomas, Rüdiger, Thomas , Ulmer, Hans Ulrich, Dunning, Alison M. , Humphreys, Manjeet K., Wang, Qin , Cox, Angela , Cross, Simon S. , Reed, Malcolm , Czene, Kamila , Ademuyiwa, Foluso O. , Hwang, Helena, Eccles, Diana M., García‐Closas, Montserrat , Figueroa, Jonine D. , Sherman, Mark E., Lissowska, Jolanta , Seynaeve, Caroline, Tollenaar, Rob A.�E.�M. , Hooning, Maartje J. , Andrulis, Irene L. , Knight, Julia A. , Glendon, Gord, Mulligan, Anna Marie , Winqvist, Robert , Pylkäs, Katri , Jukkola‐Vuorinen, Arja , Grip, Mervi, John, Esther M. , Miron, Alexander, Alnæs, Grethe Grenaker, Kristensen, Vessela, Børresen‐Dale, Anne‐Lise , Giles, Graham G. , Baglietto, Laura , McLean, Catriona , Severi, Gianluca , Kosel, Matthew L., Pankratz, V.S., Slager, Susan, Radice, Paolo , Peterlongo, Paolo , Manoukian, Siranoush , Barile, Monica, Lambrechts, Diether , Hatse, Sigrid , Dieudonné, Anne-Sophie, Christiaens, Marie-Rose, Chenevix‐Trench, Georgia , Chen, Xiaoqing, Mannermaa, Arto, Kosma, Veli‐Matti , Hartikainen, Jaana M. , Soini, Ylermi, Easton, Douglas F., Eccles, Diana , Orr, Nick , Thorne, Heather , Purrington, Kristen S. , Lambrechts, Diether , Vachon, Celine M. , Wang, Xianshu , Meindl, Alfons, Godwin, Andrew K. , Pathak, Harsh B. , Müller, Heiko , Arndt, Volker , Gogas, Helen J , Milne, Roger L. , Benı́tez, Javier , Pérez, José Ignacio Arias , Fletcher, Olivia , Broeks, Annegien , Orr, Nicholas, Anton‐Culver, Hoda , Ziogas, Argyrios , Bernstein, Leslie , Pharoah, Paul D.P. , Hall, Per N , Ambrosone, Christine B. , Eccles, Diana M., Devilee, Peter , Kristensen, Vessela N. , Kosel, Matthew , Olson, Janet E. , Beesley, Jonathan , Chen, Xiaoqing, Mannermaa, Arto, Couch, Fergus J. , Nevanlinna, H , Lambrechts, Diether , Giles, Graham G , Peterlongo, Paolo , Eccles, Diana , Swerdlow, Anthony J , Radice, Paolo , Lissowska, Jolanta , John, Esther M , Southey, Melissa C , Sinn, Peter , Muir, Kenneth , Dunning, Alison M , Lambrechts, Diether , Brenner, Hermann , Cox, Angela , Guénel, Pascal , García-Closas, Montserrat , Schmidt, Marjanka K , Severi, Gianluca , Ekici, Arif B , Hartikainen, Jaana M , Engel, Christoph , Chenevix-Trench, Georgia , Figueroa, Jonine D , Czene, Kamila , Ademuyiwa, Foluso O , Pylkäs, Katri , Yannoukakos, Drakoulis , Manoukian, Siranoush , Baglietto, Laura , Bojesen, Stig E , Purrington, Kristen S , Sharma, Priyanka , Schoemaker, Minouk J , Truong, Therese , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick
Cancer Research | February 13, 2012 | Volume: 72 | Issue: 7 | Pages: 1795-1803
Abstract The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05–1.15; P = 3.49 × 10−5] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13–1.31; P = 2.22 × 10−7). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89–1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18–1.33; P = 3.31 × 10−13]. Thus, 19p13.1 is the first triple-negative–specific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways. Cancer Res; 72(7); 1795–803. ©2012 AACR.
Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor–Positive, Lower Grade Breast Cancer
Goode, Ellen L. , García‐Closas, Montserrat , Severi, Gianluca , Hein, Rebecca, Fredericksen, Zachary, Malats, Núria , Zamora, M. Pilar , Dörk, Thilo , Schürmann, Peter , Karstens, Johann H., Hillemanns, Peter , Cox, Angela , Brock, Ian W., Elliot, Graeme, Cross, Simon S. , Seal, Sheila, Turnbull, Clare , Renwick, Anthony, Rahman, Nazneen , Shen, Chen‐Yang , Yu, Jyh‐Cherng , Huang, Chiun‐Sheng , Hou, Ming‐Feng , Nordestgaard, Børge G. , Bojesen, Stig E. , Lanng, Charlotte, Alnæs, Grethe Grenaker, Kristensen, Vessela N. , Børrensen-Dale, Anne-Lise, Hopper, John L. , Dite, Gillian S. , Apicella, Carmel, Southey, Melissa C. , Lambrechts, Diether , Yesilyurt, Betül T., Floris, Giuseppe , Leunen, Karin, Sangrajrang, Suleeporn , Gaborieau, Valérie , McKay, James , Chang‐Claude, Jenny , Wang‐Gohrke, Shan , Radice, Paolo , Peterlongo, Paolo , Manoukian, Siranoush , Barile, Monica, Giles, Graham G. , Baglietto, Laura , John, Esther M. , Miron, Alexander, Lissowska, Jolanta , Sherman, Mark E., Bogdanova, Natalia , Antonenkova, Natalia, Zalutsky, Iosif V., Rogov, Yuriy , Fasching, Peter A. , Ekici, Arif B. , Beckmann, Matthias W. , Brenner, Hermann , Stegmaier, Christa, Andrulis, Irene L. , Knight, Julia A. , Glendon, Gord, Mulligan, Anna Marie , Mannermaa, Arto, Kataja, Vesa , Kosma, Veli‐Matti , Hartikainen, Jaana M. , Meindl, Alfons , Bartram, Claus R., Schmutzler, Rita K., Thomas, Gilles D., Hoover, Robert N. , Fletcher, Olivia , Gibson, Lorna J., dos‐Santos‐Silva, Isabel , Peto, Julian, Nickels, Stefan , Flesch‐Janys, Dieter, Sawyer, Elinor J. , Tomlinson, Ian , Kerin, Michael J. , Miller, Nicola, Schmidt, Marjanka K. , Veer, Laura van ‘t , Tollenaar, Rob A.�E.�M. , Dunning, Alison M. , Pooley, Karen A. , Schneeweiß, Andreas , Sohn, Christof , Burwinkel, Barbara , Jakubowska, Anna , Lubiński, Jan , Jaworska, Katarzyna, Durda, Katarzyna, Kang, Daehee , Noh, Dong‐Young , Ahn, Sei-Hyun, Hunter, David J. , Hankinson, Susan E. , Lindström, Sara, Chen, Xiaoqing, Beesley, Jonathan, Hamann, Ute, Justenhoven, Christina , Network, for the GENICA, Winqvist, Robert , Pylkäs, Katri , Jukkola‐Vuorinen, Arja , Grip, Mervi, Hooning, Maartje J. , Hollestelle, Antoinette , Oldenburg, Rogier A., Tilanus‐Linthorst, Madeleine M.A., Хуснутдинова, Э. К. , Bermisheva, Marina , Prokofieva, Darya, Farahtdinova, Albina, Humphreys, Manjeet K., Wang, Qin , Chenevix‐Trench, Georgia , Easton, Douglas F. , Lambrechts, Diether , Milne, Roger L. , Couch, Fergus J. , Pérez, José Ignacio Arias , Benı́tez, Javier , Børrensen-Dale, Anne-Lise, Brennan, Paul , Chanock, Stephen Jacob , Figueroa, Jonine D. , Bayer, Christian , Müller, Heiko , Arndt, Volker , Mannermaa, Arto, Meindl, Alfons , Heil, Joerg , Anton‐Culver, Hoda , Ziogas, Argyrios , Broeks, Annegien , Veer, Laura J. van’t , Pharoah, Paul D.P. , Marmé, Frederik , Yoo, Keun-Young , Hankinson, Susan E. , Kraft, Peter , Chen, Xiaoqing, Harth, Volker , Network, for the GENICA, Olson, Janet E. , Wang, Xianshu , Dörk, Thilo , Lambrechts, Diether , Giles, Graham G , Peterlongo, Paolo , Hillemanns, Peter , Radice, Paolo , Lissowska, Jolanta , John, Esther M , Southey, Melissa C , Malats, Nuria , Dunning, Alison M , Jakubowska, Anna , Lambrechts, Diether , Brenner, Hermann , Cox, Angela , García-Closas, Montserrat , Schmidt, Marjanka K , Severi, Gianluca , Ekici, Arif B , Hartikainen, Jaana M , Bogdanova, Natalia V , Chenevix-Trench, Georgia , Pylkäs, Katri , Manoukian, Siranoush , Lubinski, Jan , Baglietto, Laura , Fletcher, Olivia , Bojesen, Stig E , Huang, Chiun-Sheng , Sawyer, Elinor J , Kang, Daehee
Cancer Epidemiology, Biomarkers & Prevention | October 6, 2011 | Volume: 20 | Issue: 10 | Pages: 2222-2231
Abstract Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08–1.14, P = 7 × 10−18) for invasive breast cancer and 1.10 (95% CI = 1.01–1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99–1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR = 1.16, 95% CI = 1.12–1.20, P = 1 × 10−18 vs. OR = 1.03, 95% CI = 0.99–1.07, P = 0.2 for PR-negative disease; Pheterogeneity = 2 × 10−7); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14–1.25), 1.13 (1.09–1.16), and 1.04 (0.99–1.08) for grade 1, 2, and 3/4, respectively; Ptrend = 5 × 10−7]. Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants. Cancer Epidemiol Biomarkers Prev; 20(10); 2222–31. ©2011 AACR.
Common Breast Cancer Susceptibility Loci Are Associated with Triple-Negative Breast Cancer
Stevens, Kristen N., Vachon, Celine M. , Slager, Susan, Lesnick, Timothy G. , Olswold, Curtis, Fasching, Peter A. , Miron, Penelope , Eccles, Diana , Carpenter, Jane, Winqvist, Robert , Brauch, Hiltrud , Schmidt, Marjanka K. , Cox, Angela , Cross, Simon S. , Sawyer, Elinor J. , Hartmann, Arndt, Beckmann, Matthias W. , Schulz-Wendtland, Rüdiger, Ekici, Arif B. , Tapper, William , Gerty, Susan M. , Durcan, Lorraine , Graham, Nikki , Hein, Rebecca, Nickels, Stephan, Flesch‐Janys, Dieter, Heinz, Judith , Sinn, Hans‐Peter , Konstantopoulou, Irene , Pectasides, Dimitrios , Dimopoulos, Athanasios M., Clarke, Christine L. , Balleine, Rosemary L. , Fredericksen, Zachary, Diasio, Robert B. , Ross, Eric A. , Weaver, JoEllen , Rüdiger, Thomas , Dünnebier, Thomas, Ademuyiwa, Foluso O. , Kulkarni, Swati , Pylkäs, Katri , Jukkola‐Vuorinen, Arja , Ko, Yon‐Dschun, Limbergen, Erik Van, Janssen, Hilde, Peto, Julian , Fletcher, Olivia , Giles, Graham G. , Baglietto, Laura , Verhoef, Senno, Tomlinson, Ian , Kosma, Veli‐Matti , Greco, Dario , Blomqvist, Carl , Irwanto, Astrid , Liu, Jianjun , Blows, Fiona M., Dawson, Sarah‐Jane , Margolin, Sara , Mannermaa, Arto, Martin, Nicholas G. , Montgomery, Grant W. , Lambrechts, Diether , dos‐Santos‐Silva, Isabel , Severi, Gianluca , Hamann, Ute, Easton, Douglas F., Chang‐Claude, Jenny , Yannoukakos, Drakoulis , Nevanlinna, Heli , Dimopoulos, Meletios Α. , Purrington, Kristen S. , Lambrechts, Diether , Vachon, Celine M. , Lee, Adam M. , Godwin, Andrew K. , Ambrosone, Christine B. , Fostira, Florentia , Dimopoulos, Athanasios M., Fountzilas, George , Olson, Janet E. , Pathak, Harsh B. , Försti, Asta , Beesley, Jonathan , Mannermaa, Arto, Pharoah, Paul D.P. , Wang, Xianshu , Couch, Fergus J. , Nevanlinna, H , Lambrechts, Diether , Giles, Graham G , Eccles, Diana , Dimopoulos, Meletios A , Konstantopoulou, Irene , Martin, Nicholas G , Sinn, Peter , Lambrechts, Diether , Cox, Angela , Schmidt, Marjanka K , Severi, Gianluca , Ekici, Arif B , Ademuyiwa, Foluso O , Pylkäs, Katri , Yannoukakos, Drakoulis , Baglietto, Laura , Fletcher, Olivia , Purrington, Kristen S , Brauch, Hiltrud , Sawyer, Elinor J , Liu, Jing
Cancer Research | August 15, 2011 | Volume: 71 | Issue: 19 | Pages: 6240-6249
Abstract Triple-negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiologic factors that promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome-wide association studies display heterogeneity of effect among breast cancer subtypes as defined by the status of estrogen and progesterone receptors. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple-negative breast cancer and 4,978 healthy controls. We identified six single-nucleotide polymorphisms, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.1), and rs8100241 (19p13.1), significantly associated with the risk of triple-negative breast cancer. Together, our results provide convincing evidence of genetic susceptibility for triple-negative breast cancer. Cancer Res; 71(19); 6240–9. ©2011 AACR.
Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
Antoniou, Antonis C. , Sinilnikova, Olga M., Soucy, Penny, McGuffog, Lesley, Healey, Sue, Peterlongo, Paolo , Manoukian, Siranoush , Peissel, Bernard , Zaffaroni, Daniela , Cattaneo, Elisa , Barile, Monica, Pensotti, Valeria , Pasini, Barbara , Dolcetti, Riccardo , Giannini, Giuseppe , Putignano, Anna Laura , Varesco, Liliana , Radice, Paolo , Mai, Phuong L., Greene, Mark H. , Andrulis, Irene L. , Glendon, Gord , Özçelik, Hilmi, Thomassen, Mads , Gerdes, Anne‐Marie , Kruse, Torben A., Jensen, Uffe Birk , Crüger, Dorthe Gylling, Caligo, Maria A. , Laitman, Yael , Milgrom, Roni, Friedman, Eitan , Loman, Niklas, Harbst, Katja , Lindblom, Annika , Arver, Brita, Ehrencrona, Hans , Melin, Beatrice , SWE-BRCA, Nathanson, Katherine L. , Rebbeck, Timothy R., Jakubowska, Anna , Lubiński, Jan , Huzarski, Tomasz , Byrski, Tomasz , Cybulski, Cezary, Górski, Bohdan , Osório, Ana , Hamann, Ute, Hogervorst, Frans B.L., Rookus, Matti A. , Hooning, Maartje J. , Nelen, Marcel , Luijt, Rob B. van der , Os, Theo A.M. van, Meijers‐Heijboer, Hanne , Gómez, E. , HEBON, Peock, Susan, Cook, Margaret , Frost, Debra, Platte, Radka, Leyland, Jean, Evans, D. Gareth , Lalloo, Fiona, Eeles, Rosalind A. , Izatt, Louise , Adlard, Julian , Davidson, Rosemarie, Eccles, Diana , Ong, Kai-Ren, Douglas, Fiona, Paterson, Joan, Miedzybrodzka, Zosia , EMBRACE, Buecher, Bruno , Belotti, Muriel, Tirapo, Carole, Mazoyer, Sylvie , Barjhoux, Laure, Lasset, Christine , Leroux, Dominique, Faivre, Laurence, Bronner, Myriam , Prieur, Fabienne, Noguès, Catherine , Rouleau, Étienne , Coupier, Isabelle, Frénay, Marc, Collaborators, CEMO Study, Daly, Mary B., Terry, Mary Beth , John, Esther M. , Yassin, Yosuf, Miron, Alexander, Goldgar, David E., Registry, Breast Cancer Family, Singer, Christian F., Tea, Muy‐Kheng, Pfeiler, Georg , Dressler, Anne Catharina, Hansen, Thomas van Overeem , Jønson, Lars, Ejlertsen, Bent , Barkardóttir, Rósa B. , Kirchhoff, Tomas , Offit, Kenneth, Piedmonte, Marion, Rodriguez, Gustavo C. , Small, Laurie, Boggess, John F., Blank, Stephanie V. , Basil, Jack, Montagna, Marco , Tognazzo, Silvia , Imyanitov, Evgeny , Janavičius, Ramūnas , Lázaro, Conxi , Blanco, Ignacio , Sucheston, Lara, Walsh, Christine , Oláh, Edith , Bozsik, Anikó , Teo, Soo‐Hwang , Seldon, Joyce, Beattie, Mary, Rensburg, Elizabeth J. van , Sluiter, Michelle D., Dı́ez, Orland , Schmutzler, Rita K., Wappenschmidt, Barbara , Engel, Christoph , Meindl, Alfons , Ruehl, I., Varon-Mateeva, Raymonda, Kast, Karin, Deißler, Helmut , Niederacher, Dieter , Arnold, Norbert , Gadzicki, Dorothea, Schönbuchner, Ines, Caldes, Trinidad, Hoya, Miguel de la , Nevanlinna, Heli , Aittomäki, Kristiina, Dumont, Martine , Chiquette, Jocelyne , Chen, Xiaoqing, Beesley, Jonathan, Spurdle, Amanda B. , investigators, kConFab, Ding, Yuan Chun , Fredericksen, Zachary, Simard, Jacques , Easton, Douglas F. , Chenevix‐Trench, Georgia , CIMBA, on behalf of, Sutter, Christian , Vasen, Hans F. A. , Durocher, Francine , Rahman, Nazneen , Karlsson, Per , Nordling, Margareta , Olsson, Håkan , Hoogerbrugge, Nicoline , Waisfisz, Quinten , Barton, David , Tobias, Edward S. , Jacobs, Chris , Ellis, Ian O. , Castro, Elena , Lucassen, Anneke , Gladieff, Laurence , Thorne, Heather , Stenmark‐Askmalm, Marie , Faivre, Laurence , Kartsonaki, Christiana , Lee, Andrew , Mai, Phuong L., Kaufman, Bella , Paluch–Shimon, Shani , SWE-BRCA, Domchek, Susan M. , Gronwald, Jacek , Cajal, Teresa Ramón y , Fostira, Florentia , Andrés, Raquel , Benı́tez, Javier , Asperen, Christi J. van , Devilee, Peter , HEBON, Cook, Jackie A , Kennedy, Michael John , EMBRACE, Godwin, Andrew K. , Stoppa‐Lyonnet, Dominique , Pujol, Pascal , Collaborators, CEMO Study, Hopper, John L. , Buys, Saundra S. , Registry, Breast Cancer Family, Singer, Christian F. , Azodi, Masoud , Toland, Amanda Ewart , Agata, Simona , Pharoah, Paul D.P. , Karlan, Beth Y. , Meindl, Alfons , Caldes, Trinidad, Tischkowitz, Marc D. , Chen, Xiaoqing, investigators, kConFab, Neuhausen, Susan L. , Wang, Xianshu , Pankratz, V. Shane , Couch, Fergus J. , CIMBA, on behalf of, Nevanlinna, H , Caligo, Maria A , Peterlongo, Paolo , Spurdle, Amanda B , Teo, Soo H , van Rensburg, Elizabeth J , Eccles, Diana , de la Hoya, Miguel , Diez, Orland , Radice, Paolo , Adlard, Julian , Arnold, Norbert , Eeles, Rosalind A , Ehrencrona, Hans , Evans, D Gareth , John, Esther M , van der Luijt, Rob B , Jakubowska, Anna , Nathanson, Katherine L , Bozsik, Aniko , Engel, Christoph , Lazaro, Conxi , Montagna, Marco , Simard, Jacques , Chenevix-Trench, Georgia , Huzarski, Tomasz , Faivre, Laurence , Gómez-García, Encarna B , Hansen, Thomas van Overeem , Pasini, Barbara , Manoukian, Siranoush , Lubinski, Jan , Terry, Mary Beth , Lindblom, Annika , Ellis, Ian
Human Molecular Genetics | May 19, 2011 | Volume: 20 | Issue: 16 | Pages: 3304-3321
Breast Cancer Risk Reduction and Membrane-Bound Catechol O -Methyltransferase Genetic Polymorphisms
Zhang, Jianping , Hildebrandt, Michelle, Wang, Liewei , Fredericksen, Zachary, Sellers, Thomas A. , Miller, William H. , Dixon, J. Michael , Brauch, Hiltrud , Eichelbaum, Michel , Justenhoven, Christina , Hamann, Ute , Ko, Yon, Brüning, Thomas , Chang‐Claude, Jenny , Wang‐Gohrke, Shan , Schaid, Daniel J. , Weinshilboum, Richard M. , Ji, Yuan , Olson, Janet E. , Ingle, James N. , Weinshilboum, Richard M. , Brauch, Hiltrud
Cancer Research | July 16, 2008 | Volume: 68 | Issue: 14 | Pages: 5997-6005
Abstract Catechol O-methyltransferase (COMT)-catalyzed methylation of catecholestrogens has been proposed to play a protective role in estrogen-induced genotoxic carcinogenesis. We have taken a comprehensive approach to test the hypothesis that genetic variation in COMT might influence breast cancer risk. Fifteen COMT single nucleotide polymorphisms (SNPs) selected on the basis of in-depth resequencing of the COMT gene were genotyped in 1,482 DNA samples from a Mayo Clinic breast cancer case control study. Two common SNPs in the distal promoter for membrane-bound (MB) COMT, rs2020917 and rs737865, were associated with breast cancer risk reduction in premenopausal women in the Mayo Clinic study, with allele-specific odds ratios (OR) of 0.70 [95% confidence interval (CI), 0.52–0.95] and 0.68 (95% CI, 0.51–0.92), respectively. These two SNPs were then subjected to functional genomic analysis and were genotyped in an additional 3,683 DNA samples from two independent case control studies (GENICA and GESBC). Functional genomic experiments showed that these SNPs could up-regulate transcription and that they altered DNA-protein binding patterns. Furthermore, substrate kinetic and exon array analyses suggested a role for MB-COMT in catecholestrogen inactivation. The GENICA results were similar to the Mayo case control observations, with ORs of 0.85 (95% CI, 0.72–1.00) and 0.85 (95% CI, 0.72–1.01) for the two SNPs. No significant effect was observed in the GESBC study. These studies showed that two SNPs in the COMT distal promoter were associated with breast cancer risk reduction in two of three case control studies, compatible with the results of functional genomic experiments, suggesting a role for MB-COMT in breast cancer risk. [Cancer Res 2008;68(14):5997–6005]